Human glucocorticoid receptor (hGR) promoter fragments subcloned into a vector with luciferase reporter gene were transfected into GR-expressing cell lines to investigate basal transcription activity by transient expression assays. A region with the greatest effect on transcription was identified by systematic deletions of promoter segments. Down-regulation b dexamethasone using the promoter constructs tested so far has not shown impressive repression. Gel mobility shift assays reveal that the putative regulatory sequences that have been tested so far bind nuclear factors in a specific manner. Genomic clones encoding the human mineralocorticoid receptor (hMR) were isolated to establish the gene structure of the receptor, determine the exon/intron sequences flanking the splice sites, and that of the promoter. Phylogenetic analysis of the steroid nuclear receptor superfamily reveals a least seven subfamilies and clustered receptors appear to recognize ligands of similar chemical structure. The systematic genomic mapping for a bipolar predisposing locus was continued by genetically typing 20 CNG pedigrees with more markers on additional chromosomes. A total number of 136 loci have been examined and more loci are being analyzed using highly polymorphic markers. The following genes were mapped genetically: cannabinoid receptor gene (CNR on 6q, endothelin-1 gene (EDN1) on 6p and phenylethanolamine N- methyltransferase (PNMT) on 17q.